Serum lysophosphatidic acid levels and exacerbation frequency in chronic obstructive pulmonary disease (COPD)

Introduction: Autotaxin-Lysophosphatidic acid (ATX-LPA) pathway has been associated with inflammatory lung conditions including COPD as it has pleiotropic roles in cell proliferation, lymphocyte homing and fibrosis. ATX functions primarily as lysophospholipase D to generate bioactive lipid LPA detected in blood and inflamed sites. Aims: We assessed if systemic LPA levels were associated with exacerbation frequency and severity in COPD patients. Methods: Mass spectrometry assays for LPA species (LPAs) were developed in-house using a custom lipid extraction method, and demonstrated good reproducibility and recovery. LPAs were measured in baseline serum samples from the placebo arm (n=136) of a COPD randomized controlled trial (NCT02546700). The relationship between LPA levels, baseline demographics, and other biomarkers were assessed using Mann-Whitney or Spearman method. Tertile levels of each LPA species were used to assign patients into biomarker high, mid, and low subgroups, and association with on-study exacerbation assessed by a Quasi-Poisson model. Results: Levels of LPA species were correlated with each other (Spearman rho 0.35 – 0.92), and were influenced by age, gender, region, and exacerbation history. After adjusting for these confounders, patients with the lowest tertile of LPAs had two times higher exacerbation rate in the 6-month follow-up, compared to patients with the highest tertile of LPAs (p Conclusions: These findings provide preliminary support that systemic LPAs are detectable in COPD and associate with exacerbation rate.